The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis

Abstract

Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, is highly active in patients with multiple myeloma. We studied the toxicity and efficacy of lenalidomide in patients with AL. Patients with symptomatic AL, a measurable plasma cell disorder, and adequate hematologic and renal reserve were eligible. Patients received single-agent lenalidomide. If there was no evidence of progression after 3 months or of hematologic response after 3 cycles, dexamethasone was added. Twenty-three patients were enrolled. Thirteen were previously treated. Organ involvement was cardiac (64%), renal (73%), hepatic (23%), and nerve (14%). Within the first 3 cycles of therapy, 10 patients discontinued treatment: 4 early deaths, 3 adverse events, and 3 other causes. With a median follow-up of 17 months, 10 patients responded to treatment. In these patients, responses included 9 hematologic, 4 renal, 2 cardiac, and 2 hepatic. All but one of the responders had dexamethasone added to their treatment program. The most common grade 3 or 4 adverse events at least possibly attributable to lenalidomide were neutropenia (45%), thrombocytopenia (27%), rash (18%), and fatigue (18%). In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation. (Blood. 2007;109: [465][466][467][468][469][470]

Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis

“…46 Several phase II clinical trials in relapsed/refractory patients have been performed with immunomodulatory agents or the proteasome inhibitor bortezomib as single agents or in combination with alkylating agents and steroids with promising results. 45,[47][48][49][50] However, the outcomes of these clinical trials are difficult to interpret because of the mix of patients with respect to disease status, prior initial therapy, extent of organ involvement and different ways of reporting results. For phase III studies in relapsed/refractory patients, stratification based on degree of organ disease is indicated.…”

Recent Improvements in Survival in Primary Systemic Amyloidosis and the Importance of an Early Mortality Risk Score

“…28,29 These include high-dose therapy and SCT, the combination of melphalan and dexamethasone, and more recently the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide used alone or in combination. [6][7][8][9][10][14][15][16][17][18][19][20][21][22][23][24]30,31 How much these individual interventions have changed the outcome of patients with AL remains unclear.…”

“…13 In addition to new drugs, the combination of melphalan and dexamethasone is an effective regimen for AL, and risk-adapted approaches to SCT have decreased treatment-related mortality. [14][15][16][17][18][19][20][21][22][23][24] Whether recent progress in risk stratification and treatment approaches has translated into improved survival for these patients is unclear. Therefore, we undertook this study to examine trends in survival of patients with AL over time, with an emphasis on identifying patient characteristics predicting outcome.…”

Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis

“…This HCR rate is substantially higher than that observed with a single cycle of HDM/SCT (42%), 3 with a combination of oral melphalan and dexamethasone (33%) 13 and with lenalidomide and dexamethasone (29%). 14,15 For all 62 patients enrolling in the trial, the HCR rate was 56% (35/62) by intention-to-treat, as three additional patients achieved an HCR with one cycle of HDM/SCT after being removed from the tandem treatment protocol. Thus, for patients who can tolerate this treatment approach, such treatment appears to result in the highest HCR rate of any treatment for AL amyloidosis reported to date.…”